CPX-351 Plus Enasidenib for Relapsed AML
brief summary
This trial evaluates how well CPX-351 and enasidenib work in treating patients with acute myeloid leukemia characterized by IHD2 mutation. Drugs used in chemotherapy, such as CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CPX-351 and enasidenib may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.
detailed description
PRIMARY OBJECTIVE:
I. To estimate the remission rate (defined as complete remission \[CR\]/ CR with incomplete hematologic recovery \[CRi\]) of the combination of liposome-encapsulated daunorubicin-cytarabine (CPX-351) plus enasidenib mesylate (enasidenib) in adults with relapsed acute myeloid leukemia (AML) characterized by a 2-hydroxyglutarate (2-HG) producing IDH2 mutations that include IDH2\^R172 and IDH2\^R140.
SECONDARY OBJECTIVES:
I. To evaluate persistent severe hematologic toxicity at induction day 60 in patients with a morphologic leukemia-free state (bone marrow blasts \< 5%).
II. To evaluate delayed CR/CRi with enasidenib maintenance in participants with stable disease after induction with CPX-351.
III. To estimate the rate of CR plus complete remission with partial hematologic recovery (CRp) of the combination of CPX-351 plus enasidenib.
IV. To evaluate time to return of normal hematopoiesis after induction therapy. V. To evaluate 30- and 60-day survival. VI. To evaluate CPX-351 plus enasidenib as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT).
EXPLORATORY OBJECTIVES:
I. To determine the co-existing mutations that are present with the IDH2 mutation and describe those that are present in patients who achieve CR/CRi.
II. To determine the depth of molecular response to induction by minimal residual disease (MRD) using next generation sequencing.
III. To estimate the subclinical cardiotoxicity of CPX-351 as measured by troponin I, electrocardiography (ECG), and echocardiography.
OUTLINE:
INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5, and enasidenib mesylate orally (PO) on days 10-60 in the absence of disease progression or unacceptable toxicity. Patients whose bone marrow is not hypoplastic receive re-induction including liposome-encapsulated daunorubicin-cytarabine IV on days 1 and 3, and enasidenib mesylate PO on days 8-60 in the absence of disease progression or unacceptable toxicity.
official title
CPX-351 Plus Enasidenib for Relapsed Acute Myelogenous Leukemia Characterized by the IDH2 Mutation